Genetic discoveries are in the news and on their way
By W. Gregory Feero, MD, PhD
Have you looked at your local newspaper today? Odds are that there is a news tidbit related to a genetic discovery buried within its pages. Five years ago, the discovery might have been about a clinical fascinoma, but today it's more likely to relate to a bread-and-butter disorder treated in the primary care setting. Consider the following recent examples of discoveries about genetic variants—inherited changes in DNA sequence at specific points in the genome. Each set of discoveries concerned a common disease and was covered by the mainstream media:
Diabetes. Over the last few months, seven new common genetic variants contributing to type 2 diabetes risk have been discovered, bringing the total to 10 (and perhaps more very soon). At least one model suggests that individuals inheriting the highest risk variants are four times more likely to develop type 2 diabetes than those inheriting the lowest risk variants.
Prostate cancer. In the last year, at least seven new genetic variants contributing to prostate cancer risk in the general population have been described. Inheritance of a subset of these variants very likely explains much of the disproportionate burden of prostate cancer among young African-American men.
Macular degeneration. In the last two years, researchers have reported on five common genetic variants contributing to the risk of age-related macular degeneration (AMD). Individuals inheriting the high-risk version of all five genetic markers appear to have a 250-fold increased risk of developing AMD compared with those that inherited the lowest risk variants.
Science has only recently developed tools that allow the successful study of complex disorders—those in which multiple genes and environment strongly interact.
A few of you cynical types out there might be thinking that the genetics research community has at long last recognized the importance of common disease. In truth, science has only recently developed tools that allow the successful study of complex disorders—those in which multiple genes and environment strongly interact. The information windfall has roots in the convergence of several factors, including the exponentially decreasing cost of sequencing DNA and the completion of a tool for studying the human genome called the HapMap.
Making a long and fascinating story short, it is now feasible to look at statistical associations between disease status and large numbers of genetic variants across the genome in large numbers of people. Amazingly, what five years ago would literally have taken billions of dollars, several large labs and years to complete can now be done by one lab group in a matter of months for less than $1 million.
This approach to learning about the genetics of common, complex disorders is known as a genome-wide association study (GWAS). Properly applied, the GWAS approach has incredible power to detect common genetic variants that contribute to small or large increases in disease risk in any one individual. The scientific yield is already enormous and the end is not in sight. In fact the examples cited above are the beginning drops of what should be a flood of such reports in the next few years.
But, how and how quickly will the data translate to clinical applications? Already at least one company has developed and is planning to market a genetic test for predicting the risk of developing diabetes. Numerous companies are targeting newly identified genes for rational drug design. Studies are underway to examine how testing patients with panels of genetic risk markers for multiple common diseases may improve patient care as well as how patients themselves will react to this type of testing.
Can you order testing for your patients based on the results of knowledge gleaned from GWAS-type studies today? Actually, yes. Should you? That remains to be seen. What is starkly apparent is that patient care will be strongly influenced by this tide of information, and primary care physicians will have a front-row seat.
W. Gregory Feero, MD, PhD, a family physician with a doctorate in human genetics, is senior advisor for genomic medicine in the Office of the Director at the NIH's National Human Genome Research Institute.
Internist Archives Quick Links
Internal Medicine Meeting 2015 Digital Presentations
Choose from over 170 recorded Scientific Program Sessions and Pre-Courses. Available in a variety of packages and formats so you can choose the combination that works best for you.